EP0274445A2 - Additif de milieu de culture sans sérum et son utilisation - Google Patents
Additif de milieu de culture sans sérum et son utilisation Download PDFInfo
- Publication number
- EP0274445A2 EP0274445A2 EP19880300121 EP88300121A EP0274445A2 EP 0274445 A2 EP0274445 A2 EP 0274445A2 EP 19880300121 EP19880300121 EP 19880300121 EP 88300121 A EP88300121 A EP 88300121A EP 0274445 A2 EP0274445 A2 EP 0274445A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- serum
- additive
- growth medium
- free growth
- medium additive
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000654 additive Substances 0.000 title claims abstract description 47
- 230000000996 additive effect Effects 0.000 title claims abstract description 47
- 239000001963 growth medium Substances 0.000 title claims abstract description 35
- 210000004027 cell Anatomy 0.000 claims abstract description 27
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052742 iron Inorganic materials 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 239000013522 chelant Substances 0.000 claims abstract description 9
- 239000011573 trace mineral Substances 0.000 claims abstract description 9
- 235000013619 trace mineral Nutrition 0.000 claims abstract description 9
- 238000012360 testing method Methods 0.000 claims abstract description 8
- GIXWDMTZECRIJT-UHFFFAOYSA-N aurintricarboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=CC1=C(C=1C=C(C(O)=CC=1)C(O)=O)C1=CC=C(O)C(C(O)=O)=C1 GIXWDMTZECRIJT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 210000004408 hybridoma Anatomy 0.000 claims abstract description 6
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 4
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract 12
- 239000003102 growth factor Substances 0.000 claims abstract 3
- 210000002966 serum Anatomy 0.000 claims description 18
- 239000002609 medium Substances 0.000 claims description 15
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 238000004113 cell culture Methods 0.000 claims description 7
- 230000012010 growth Effects 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 230000010261 cell growth Effects 0.000 claims description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
- 150000002739 metals Chemical class 0.000 claims description 6
- 239000007640 basal medium Substances 0.000 claims description 5
- 239000012980 RPMI-1640 medium Substances 0.000 claims description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 3
- 239000007995 HEPES buffer Substances 0.000 claims description 3
- 102000004877 Insulin Human genes 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 2
- -1 Na-pyruvate Chemical compound 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- LMSDCGXQALIMLM-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;iron Chemical group [Fe].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O LMSDCGXQALIMLM-UHFFFAOYSA-N 0.000 claims 3
- 239000012141 concentrate Substances 0.000 claims 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 1
- 229930182816 L-glutamine Natural products 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims 1
- 229910052804 chromium Inorganic materials 0.000 claims 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 229910052748 manganese Inorganic materials 0.000 claims 1
- 229920001993 poloxamer 188 Polymers 0.000 claims 1
- 238000012372 quality testing Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 102000004338 Transferrin Human genes 0.000 description 4
- 108090000901 Transferrin Proteins 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000012679 serum free medium Substances 0.000 description 4
- 239000012581 transferrin Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 231100000167 toxic agent Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- FZIPCQLKPTZZIM-UHFFFAOYSA-N 2-oxidanylpropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FZIPCQLKPTZZIM-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 206010022971 Iron Deficiencies Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000006175 metal-ion buffer Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
- C12N5/0037—Serum-free medium, which may still contain naturally-sourced components
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
- C12N2500/14—Calcium; Ca chelators; Calcitonin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/24—Iron; Fe chelators; Transferrin
Definitions
- the present invention concerns a serum-free medium additive which may be used when culturing cells which require iron in the growth medium.
- the serum-free growth medium additive according to the invention may additionally be used to test the quality of growth media.
- the serum-free additive By using the serum-free additive according to the present invention, the above disadvantages are avoided, and such a medium will in addition be very well suited for culturing and storing cells and tissued in vitro.
- a complete medium with this additive will be precisely defined, be serum free and protein-free (except for a possible small quantity of insulin which is required by some cells, and which is used where necessary) and contain iron and trace elements in the form of stabilized chelated elements or compounds with transferrin or lipids being present. It is also very inexpensive to produce the additive according to the invention.
- the medium according to the invention was produced, on the bases of a Fe/trace element buffer of synthetic non-protein chelants and such that the main problem, precipitation of metals at 37°C (see above), was solved by adding certain chelants which in combination in solution have very different and unique properties compared to each chelant alone.
- the serum-free growth medium additive of the invention comprises
- An additive according to the present invention may, e.g., be prepared by adding a concentrated solution of each of the components to pure water (it is of great importance to use water of highest possible purity such as for instance "Travenol" sterile water, when preparing the medium according to the invention).
- a concentrated mixture is given below, where there is produced a composition which may be used in a 1000-fold concentration:
- the pH of the composition is preferably adjusted to 4.5-5.0.
- trace elements may, e.g., be carried out be the aid of a stock solution which may be prepared as follows. That solution will have a 100 000 fold concentration of that to be used in the medium.
- Zn, Cu and chelants EDTA and citrate
- the final pH should be between 4.0 and 4.5.
- composition of trace elements may contain elements other than those given in the table above, depending on the requirements of the tissue of cell types to be used.
- the additive according to the invention may, besides the components mentioned hereinbefore contain growth stimulating and necessary compounds for cell growth.
- Such compounds may comprise for instance the surfactant "Pluronic" F 68 (20 mg/1), D-glucose (2.5 g/1), L-glutamine (2 mM), Na-pyruvate (1 nM), insulin (0.5 mg/1) or ethanolamine (20 ⁇ M). All the concentrations shown in brackets refer to final concentrations.
- a composition for the addition of the compounds mentioned (except of ethanolamine which is a liquid at room temperature) may be produced as a dry product and as such this may be stored during long periods of time, up to several years.
- Ethanolamine may, if necessary, be added to the medium to a desired concentration when using the composition. Ethanolamine is most frequently used in experiments with hybridoma cells when producing monoclonal antibodies.
- a preferred basal medium to which the growth medium additive according to the present invention may be added is RPMI 1640 containing 2.5g/l NaHCO3 and 20mM HEPES (N-2-hydroxyethylpiperazine-N,N ⁇ -2-ethanesulphonic acid).
- Preferred cell cultures for which the serum-free additive according to the invention have proven to be especially useful is the L 929 mouse fibroblast cell line, the HeLa hyman tumor cell line, various mouse and human B hybridoma cells which all produce monoclonal anti-bodies in quantities corresponding to growth in serum-containing cultures, and human monocytes which differentiate to developed macrophages during 7 days while keeping their complement receptors.
- a particularly preferred use of the present additive is carried out with fast-growing types of cells for testing the quality of various types of media.
- the growth medium additive according to the invention together with fast-growing cells as mentioned may be incorporated into a test-kit comprising, e.g., the additive (serum substitute) according to the invention, frozen cells (for instance on frozen carbondioxide) and optionally a medium (e.g. RPMI 1640) and culture equipment of plastics or other suitable material.
- a test-kit comprising, e.g., the additive (serum substitute) according to the invention, frozen cells (for instance on frozen carbondioxide) and optionally a medium (e.g. RPMI 1640) and culture equipment of plastics or other suitable material.
- Preferred fast-growing cells for use in testing fullg growth media are cells of a fast-growing cell line of which a cell culture has been deposited at the European Collection of Animal Cell Cultures, Porton Down, Salisbury, Wiltshire SP4 0JG on November 20, 1986, under the accession number 86112001.
- This cell type is a special kind of fast-growing cell type of hybridoma cells prepared by the fusion of p3U1 tumor cells with B-lymphocytes.
- This cell line has proven to be especially useful at quality testing of full growth media and as such is a particular aspect of the present invention.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Plant Substances (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT88300121T ATE92098T1 (de) | 1987-01-09 | 1988-01-08 | Serumfreie kulturmittelzutat und ihre verwendung. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO870095 | 1987-01-09 | ||
| NO870095A NO162160C (no) | 1987-01-09 | 1987-01-09 | Serumfritt vekstmedium, samt anvendelse derav. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0274445A2 true EP0274445A2 (fr) | 1988-07-13 |
| EP0274445A3 EP0274445A3 (en) | 1989-12-13 |
| EP0274445B1 EP0274445B1 (fr) | 1993-07-28 |
Family
ID=19889567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19880300121 Expired - Lifetime EP0274445B1 (fr) | 1987-01-09 | 1988-01-08 | Additif de milieu de culture sans sérum et son utilisation |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US5045467A (fr) |
| EP (1) | EP0274445B1 (fr) |
| JP (2) | JPH0697996B2 (fr) |
| KR (1) | KR880009124A (fr) |
| AT (1) | ATE92098T1 (fr) |
| AU (1) | AU596491B2 (fr) |
| BR (1) | BR8800040A (fr) |
| CA (1) | CA1321961C (fr) |
| DE (1) | DE3882540T2 (fr) |
| DK (1) | DK169765B1 (fr) |
| ES (1) | ES2008411A6 (fr) |
| FI (1) | FI87230C (fr) |
| IL (1) | IL85026A (fr) |
| IT (1) | IT1215675B (fr) |
| NO (1) | NO162160C (fr) |
| NZ (1) | NZ223139A (fr) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01153085A (ja) * | 1987-10-29 | 1989-06-15 | E I Du Pont De Nemours & Co | ハイブリドーマ増殖用培地 |
| EP0432952A1 (fr) * | 1989-12-07 | 1991-06-19 | Snow Brand Milk Products Co., Ltd. | Milieu de culture sans sérum |
| WO1993000423A1 (fr) * | 1991-06-21 | 1993-01-07 | Novo Nordisk A/S | Additif pour milieu de culture a base de chelate de fer |
| WO1994002592A1 (fr) * | 1992-07-24 | 1994-02-03 | Celltech Limited | Culture de cellules animales |
| WO1994025599A1 (fr) * | 1993-04-26 | 1994-11-10 | Biotechnolog Forschung Gmbh | Lignees cellulaires de mammiferes et procede de preparation de glycoproteines |
| WO1998024883A3 (fr) * | 1996-12-04 | 1998-10-01 | Medi Cult As | Milieux de cultures cellulaires sans serum |
| EP0872487A3 (fr) * | 1997-04-18 | 1999-10-27 | Bayer Corporation | Préparation de facteur VIII recombinant en milieu sans protéine |
| WO2001016294A3 (fr) * | 1999-08-27 | 2001-09-07 | Invitrogen Corp | Composes de liaison metallique et leur utilisation dans des compositions de milieu de culture cellulaire |
| EP0929662A4 (fr) * | 1996-03-18 | 2002-12-04 | Univ Pittsburgh | Milieux de culture cellulaire pour cellules de mamiferes |
| US6767741B1 (en) | 1999-08-27 | 2004-07-27 | Invitrogen Corporation | Metal binding compounds and their use in cell culture medium compositions |
| EP1482031A1 (fr) * | 1996-08-30 | 2004-12-01 | Invitrogen Corporation | Milieu de culture de cellules de mammifères exempt de sérum |
| US20110212523A1 (en) * | 2008-11-11 | 2011-09-01 | Yukio Kato | Differentiation-inducing culture medium additive and use thereof |
| EP2390263A1 (fr) | 2005-08-26 | 2011-11-30 | Ares Trading S.A. | Procédé pour la préparation d'interféron bêta glycosylé |
| EP3122770A4 (fr) * | 2014-03-23 | 2017-08-23 | Advantech Bioscience Farmacêutica Ltda. | Amélioration de l'expression de protéines recombinantes avec du cuivre |
| CN110835622A (zh) * | 2018-08-16 | 2020-02-25 | 上海药明生物技术有限公司 | 用于调节哺乳动物细胞乳酸代谢的培养基及其应用 |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8801537D0 (sv) * | 1988-04-26 | 1988-04-26 | Ellco Food Ab | Cellodlingsmedium samt forfarande for dess framstellning |
| US5378612A (en) * | 1990-05-11 | 1995-01-03 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Culture medium for production of recombinant protein |
| US5434185A (en) * | 1993-05-17 | 1995-07-18 | The University Of Kentucky Research Foundation | Method for inhibiting angiogenesis with aurintricarboxylic acid, its analogues or salts |
| US5405772A (en) * | 1993-06-18 | 1995-04-11 | Amgen Inc. | Medium for long-term proliferation and development of cells |
| US5846529A (en) * | 1993-08-23 | 1998-12-08 | Nexell Therapeutics, Inc. | Infusion of neutrophil precursors for treatment of neutropenia |
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| JP6473079B2 (ja) | 2012-05-02 | 2019-02-20 | ライフ テクノロジーズ コーポレーション | 高密度増殖およびトランスフェクション培地並びに発現増強物質の固有の組み合わせを用いる、哺乳類細胞における高収率一過性発現 |
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| EP0314496A3 (fr) * | 1987-10-29 | 1989-08-30 | E.I. Du Pont De Nemours And Company | Production d'hybridomes |
| JPH01153085A (ja) * | 1987-10-29 | 1989-06-15 | E I Du Pont De Nemours & Co | ハイブリドーマ増殖用培地 |
| EP0432952A1 (fr) * | 1989-12-07 | 1991-06-19 | Snow Brand Milk Products Co., Ltd. | Milieu de culture sans sérum |
| WO1993000423A1 (fr) * | 1991-06-21 | 1993-01-07 | Novo Nordisk A/S | Additif pour milieu de culture a base de chelate de fer |
| WO1994002592A1 (fr) * | 1992-07-24 | 1994-02-03 | Celltech Limited | Culture de cellules animales |
| US6593140B1 (en) | 1992-07-24 | 2003-07-15 | Lonza Group, Ag | Animal cell culture |
| WO1994025599A1 (fr) * | 1993-04-26 | 1994-11-10 | Biotechnolog Forschung Gmbh | Lignees cellulaires de mammiferes et procede de preparation de glycoproteines |
| EP0929662A4 (fr) * | 1996-03-18 | 2002-12-04 | Univ Pittsburgh | Milieux de culture cellulaire pour cellules de mamiferes |
| US8455246B2 (en) | 1996-08-30 | 2013-06-04 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| US8198084B2 (en) | 1996-08-30 | 2012-06-12 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| US9321996B2 (en) | 1996-08-30 | 2016-04-26 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| US8815573B2 (en) | 1996-08-30 | 2014-08-26 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| EP1482031A1 (fr) * | 1996-08-30 | 2004-12-01 | Invitrogen Corporation | Milieu de culture de cellules de mammifères exempt de sérum |
| EP2218775A1 (fr) * | 1996-08-30 | 2010-08-18 | Life Technologies Corporation | Méthode de production d'un polypeptide in vitro dans une cellule de mammifère dans un milieu de culture sans sérum and sans protéines |
| EP2243827A1 (fr) * | 1996-08-30 | 2010-10-27 | Life Technologies Corporation | Milieu de culture de cellules de mammifères exempt de sérum et ses utilisations |
| US8785194B2 (en) | 1996-08-30 | 2014-07-22 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| WO1998024883A3 (fr) * | 1996-12-04 | 1998-10-01 | Medi Cult As | Milieux de cultures cellulaires sans serum |
| EP0872487A3 (fr) * | 1997-04-18 | 1999-10-27 | Bayer Corporation | Préparation de facteur VIII recombinant en milieu sans protéine |
| WO2001016294A3 (fr) * | 1999-08-27 | 2001-09-07 | Invitrogen Corp | Composes de liaison metallique et leur utilisation dans des compositions de milieu de culture cellulaire |
| US6767741B1 (en) | 1999-08-27 | 2004-07-27 | Invitrogen Corporation | Metal binding compounds and their use in cell culture medium compositions |
| EP2390263A1 (fr) | 2005-08-26 | 2011-11-30 | Ares Trading S.A. | Procédé pour la préparation d'interféron bêta glycosylé |
| US20110212523A1 (en) * | 2008-11-11 | 2011-09-01 | Yukio Kato | Differentiation-inducing culture medium additive and use thereof |
| EP3122770A4 (fr) * | 2014-03-23 | 2017-08-23 | Advantech Bioscience Farmacêutica Ltda. | Amélioration de l'expression de protéines recombinantes avec du cuivre |
| CN110835622A (zh) * | 2018-08-16 | 2020-02-25 | 上海药明生物技术有限公司 | 用于调节哺乳动物细胞乳酸代谢的培养基及其应用 |
| CN110835622B (zh) * | 2018-08-16 | 2021-04-27 | 上海药明生物技术有限公司 | 用于调节哺乳动物细胞乳酸代谢的培养基及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ223139A (en) | 1991-09-25 |
| DK169765B1 (da) | 1995-02-20 |
| DE3882540T2 (de) | 1993-11-18 |
| ATE92098T1 (de) | 1993-08-15 |
| DK678687D0 (da) | 1987-12-22 |
| IL85026A (en) | 1992-09-06 |
| ES2008411A6 (es) | 1989-07-16 |
| FI875793L (fi) | 1988-07-10 |
| FI875793A0 (fi) | 1987-12-31 |
| AU596491B2 (en) | 1990-05-03 |
| JPS63279786A (ja) | 1988-11-16 |
| DK678687A (da) | 1988-07-10 |
| DE3882540D1 (de) | 1993-09-02 |
| IT1215675B (it) | 1990-02-22 |
| FI87230C (fi) | 1992-12-10 |
| KR880009124A (ko) | 1988-09-14 |
| EP0274445B1 (fr) | 1993-07-28 |
| NO870095L (no) | 1988-07-11 |
| NO870095D0 (no) | 1987-01-09 |
| JPH0697996B2 (ja) | 1994-12-07 |
| FI87230B (fi) | 1992-08-31 |
| US5045467A (en) | 1991-09-03 |
| NO162160C (no) | 1989-11-15 |
| CA1321961C (fr) | 1993-09-07 |
| JP2524313B2 (ja) | 1996-08-14 |
| US5045454A (en) | 1991-09-03 |
| AU1011588A (en) | 1988-07-14 |
| NO162160B (no) | 1989-08-07 |
| IL85026A0 (en) | 1988-06-30 |
| EP0274445A3 (en) | 1989-12-13 |
| JPH06292570A (ja) | 1994-10-21 |
| IT8819024A0 (it) | 1988-01-08 |
| BR8800040A (pt) | 1988-08-02 |
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